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Investigational New Drugs

, Volume 31, Issue 5, pp 1321–1329 | Cite as

Phase II clinical study of modified FOLFOX7 (intermittent oxaliplatin administration) plus bevacizumab in patients with unresectable metastatic colorectal cancer—CRAFT study

  • Tohru TezukaEmail author
  • Chikuma Hamada
  • Hideyuki Ishida
  • Mitsuru Ooshiro
  • Hiroshi Matsuoka
  • Shingo Kawasaki
  • Hideyuki Mishima
  • Kotaro Maeda
  • Junichi Sakamoto
  • Keiji Koda
PHASE II STUDIES

Summary

Purpose Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen. Methods Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m2, levofolinate [l-LV] 200 mg/m2, 5-fluorouracil [5-FU] 2400 mg/m2) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration. Results Fifty-two patients were enrolled, with median age of 64 years (range, 36–74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin. Conclusion By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy.

Keywords

Oxaliplatin Bevacizumab Stop-and-go Modified FOLFOX7 Metastatic colorectal cancer 

Notes

Acknowledgments

We thank the staff and patients of the following participating institutions: Chiba Medical Center, Chiba University, Chibaken Saiseikai Narashino Hospital, Fujita Health University Hospital, Fukaya Red Cross Hospital, Kimitsu Chuo Hospital, Kumamoto University Hospital, Kurume University, Matsudo City Hospital, Minoh City Hospital, Nippon Medical School Chiba Hokusoh Hospital, Saishukan Hospital, Saitama Medical Center, Seirei Sakura Citizen Hospital, Teikyo University Chiba Medical Center, Toho University Sakura Medical Center, Tokyo Women’s Medical University, Yokoyama Gastrointestinal Hospital, and ECRIN (Epidemiological and Clinical Research Information Network) for their support.

Conflict of interest

We declare that we have no conflicts of interest.

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Copyright information

© The Author(s) 2013

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Authors and Affiliations

  • Tohru Tezuka
    • 1
    Email author
  • Chikuma Hamada
    • 2
  • Hideyuki Ishida
    • 3
  • Mitsuru Ooshiro
    • 4
  • Hiroshi Matsuoka
    • 5
  • Shingo Kawasaki
    • 6
  • Hideyuki Mishima
    • 7
  • Kotaro Maeda
    • 5
  • Junichi Sakamoto
    • 8
  • Keiji Koda
    • 1
  1. 1.Department of SurgeryTeikyo University Chiba Medical CenterIchihara CityJapan
  2. 2.Faculty of EngineeringTokyo University of ScienceTokyoJapan
  3. 3.Department of Digestive Tract and General Surgery, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  4. 4.Department of SurgeryToho University Sakura Medical CenterChibaJapan
  5. 5.Department of SurgeryFujita Health University HospitalAichiJapan
  6. 6.Department of SurgerySaishukan HospitalAichiJapan
  7. 7.Aichi Medical University Cancer CenterAichiJapan
  8. 8.Tokai Central HospitalGifuJapan

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